Medium-chain Triglycerides Inhibit Long-chain Triglyceride-induced GIP Secretion Through GPR120-dependent Inhibition of CCK

Overview

Journal iScience

Publisher Cell Press

Date 2021 Sep 1

PMID 34466786

Citations 10

Authors

Yuki Murata

Norio Harada

Shigenobu Kishino

Kanako Iwasaki

Eri Ikeguchi-Ogura

Shunsuke Yamane

Tomoko Kato

Yoshinori Kanemaru

Akiko Sankoda

Tomonobu Hatoko

Sakura Kiyobayashi

Jun Ogawa

Akira Hirasawa

Nobuya Inagaki

Affiliations

Soon will be listed here.

Abstract

Long-chain triglycerides (LCTs) intake strongly stimulates GIP secretion from enteroendocrine K cells and induces obesity and insulin resistance partly due to GIP hypersecretion. In this study, we found that medium-chain triglycerides (MCTs) inhibit GIP secretion after single LCT ingestion and clarified the mechanism underlying MCT-induced inhibition of GIP secretion. MCTs reduced the CCK effect after single LCT ingestion in wild-type (WT) mice, and a CCK agonist completely reversed MCT-induced inhibition of GIP secretion. studies showed that medium-chain fatty acids (MCFAs) inhibit long-chain fatty acid (LCFA)-stimulated CCK secretion and increase in intracellular Ca concentrations through inhibition of GPR120 signaling. Long-term administration of MCTs reduced obesity and insulin resistance in high-LCT diet-fed WT mice, but not in high-LCT diet-fed -knockout mice. Thus, MCT-induced inhibition of GIP hypersecretion reduces obesity and insulin resistance under high-LCT diet feeding condition.

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References

Isaacs P, Ladas S, Forgacs I, Dowling R, Ellam S, Adrian T . Comparison of effects of ingested medium- and long-chain triglyceride on gallbladder volume and release of cholecystokinin and other gut peptides. Dig Dis Sci. 1987; 32(5):481-6. DOI: 10.1007/BF01296030. View

Sankoda A, Harada N, Kato T, Ikeguchi E, Iwasaki K, Yamane S . Free fatty acid receptors, G protein-coupled receptor 120 and G protein-coupled receptor 40, are essential for oil-induced gastric inhibitory polypeptide secretion. J Diabetes Investig. 2019; 10(6):1430-1437. PMC: 6825923. DOI: 10.1111/jdi.13059. View

Takeuchi H, Noguchi O, Sekine S, Kobayashi A, Aoyama T . Lower weight gain and higher expression and blood levels of adiponectin in rats fed medium-chain TAG compared with long-chain TAG. Lipids. 2007; 41(2):207-12. DOI: 10.1007/s11745-006-5089-3. View

Oh D, Talukdar S, Bae E, Imamura T, Morinaga H, Fan W . GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell. 2010; 142(5):687-98. PMC: 2956412. DOI: 10.1016/j.cell.2010.07.041. View

Murata Y, Harada N, Yamane S, Iwasaki K, Ikeguchi E, Kanemaru Y . Medium-chain triglyceride diet stimulates less GIP secretion and suppresses body weight and fat mass gain compared with long-chain triglyceride diet. Am J Physiol Endocrinol Metab. 2019; 317(1):E53-E64. DOI: 10.1152/ajpendo.00200.2018. View

Kieffer T . Gastro-intestinal hormones GIP and GLP-1. Ann Endocrinol (Paris). 2004; 65(1):13-21. DOI: 10.1016/s0003-4266(04)95625-9. View

Sun Q, Hirasawa A, Hara T, Kimura I, Adachi T, Awaji T . Structure-activity relationships of GPR120 agonists based on a docking simulation. Mol Pharmacol. 2010; 78(5):804-10. DOI: 10.1124/mol.110.066324. View

Kuhre R, Albrechtsen N, Deacon C, Balk-Moller E, Rehfeld J, Reimann F . Peptide production and secretion in GLUTag, NCI-H716, and STC-1 cells: a comparison to native L-cells. J Mol Endocrinol. 2016; 56(3):201-11. PMC: 7212058. DOI: 10.1530/JME-15-0293. View

You Y, Ling P, Qu J, Bistrian B . Effects of medium-chain triglycerides, long-chain triglycerides, or 2-monododecanoin on fatty acid composition in the portal vein, intestinal lymph, and systemic circulation in rats. JPEN J Parenter Enteral Nutr. 2008; 32(2):169-75. PMC: 3202979. DOI: 10.1177/0148607108314758. View

10.

Liddle R, Goldfine I, Rosen M, Taplitz R, Williams J . Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction. J Clin Invest. 1985; 75(4):1144-52. PMC: 425438. DOI: 10.1172/JCI111809. View

11.

McClean P, Irwin N, Cassidy R, Holst J, Gault V, Flatt P . GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet. Am J Physiol Endocrinol Metab. 2007; 293(6):E1746-55. DOI: 10.1152/ajpendo.00460.2007. View

12.

Bray G, Popkin B . Dietary fat intake does affect obesity!. Am J Clin Nutr. 1998; 68(6):1157-73. DOI: 10.1093/ajcn/68.6.1157. View

13.

Nakamoto K, Nishinaka T, Matsumoto K, Kasuya F, Mankura M, Koyama Y . Involvement of the long-chain fatty acid receptor GPR40 as a novel pain regulatory system. Brain Res. 2011; 1432:74-83. DOI: 10.1016/j.brainres.2011.11.012. View

14.

Preitner F, Ibberson M, Franklin I, Binnert C, Pende M, Gjinovci A . Gluco-incretins control insulin secretion at multiple levels as revealed in mice lacking GLP-1 and GIP receptors. J Clin Invest. 2004; 113(4):635-45. PMC: 338268. DOI: 10.1172/JCI20518. View

15.

Iwasaki K, Harada N, Sasaki K, Yamane S, Iida K, Suzuki K . Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion. Endocrinology. 2014; 156(3):837-46. DOI: 10.1210/en.2014-1653. View

16.

Kim S, Nian C, Karunakaran S, Clee S, Isales C, McIntosh C . GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. PLoS One. 2012; 7(7):e40156. PMC: 3388996. DOI: 10.1371/journal.pone.0040156. View

17.

Dragano N, Solon C, Ramalho A, de Moura R, Razolli D, Christiansen E . Polyunsaturated fatty acid receptors, GPR40 and GPR120, are expressed in the hypothalamus and control energy homeostasis and inflammation. J Neuroinflammation. 2017; 14(1):91. PMC: 5405534. DOI: 10.1186/s12974-017-0869-7. View

18.

Ichimura A, Hirasawa A, Poulain-Godefroy O, Bonnefond A, Hara T, Yengo L . Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature. 2012; 483(7389):350-4. DOI: 10.1038/nature10798. View

19.

Luo J, Swaminath G, Brown S, Zhang J, Guo Q, Chen M . A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents. PLoS One. 2012; 7(10):e46300. PMC: 3467217. DOI: 10.1371/journal.pone.0046300. View

20.

Petrie J, Guzik T, Touyz R . Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. Can J Cardiol. 2018; 34(5):575-584. PMC: 5953551. DOI: 10.1016/j.cjca.2017.12.005. View